The clinical utility and costs of whole-genome sequencing to detect cancer susceptibility variants—a multi-site prospective cohort study

Genome Medicine

Research

Melissa J. Monnik¹  Nicola K. Poplawski²  Rachel L. Austin³  Annabel Goodwin⁴  Emilia L. Ip⁵  Amy E. McCart Reed⁶  Hilda A. Pickett⁷  Catherine Kiraly-Borri⁸  Ingrid M. Winship⁹  Sarah Norris^1,10  Uwe Dressel^1,11  Robyn L. Ward^1,12  Mohammad K. Al-Shinnag^1,13  Helen G. Mar Fan^1,13  Chiyan Lau^1,14  Abiramy Ragunathan^1,15  Rachel D. Susman^1,16  Megan J. Higgins^1,16  Simon L. Troth^1,16  Cassandra B. Nichols^1,17  Sharron L. Townshend^1,17  Nicholas S. Pachter^1,18  Marion T. Harris^1,19  Elisa J. Cops^2,20  Maie Walsh^2,20  Alison H. Trainer^2,21  Paul A. James^2,22  Katherine M. Tucker^2,23  Rachel A. Williams^2,23  Conrad Leonard^2,24  John V. Pearson^2,24  Oliver Holmes^2,24  Qinying Xu^2,24  Felicity Newell^2,24  Scott Wood^2,24  Michael T. Parsons^2,24  Lambros T. Koufariotis^2,24  Georgina E. Hollway^2,24  Vanessa Lakis^2,24  Emma Tudini^2,25  Miranda E. Vidgen^2,25  Cristina Fortuno^2,26  Daffodil M. Canson^2,26  Nicola Waddell^2,26  Dylan M. Glubb^2,26  Amanda B. Spurdle^2,26  Aimee L. Davidson^2,26  Jo Burke^2,27  Michael W. Millward^2,27  Julia L. Mansour^2,27  Mathew J. Wallis^2,28 

[1] Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, SA, Australia;Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, SA, Australia;Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia;Australian Genomics, Melbourne, VIC, Australia;Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia;Cancer Genetics Department, Royal Prince Alfred Hospital, Sydney, NSW, Australia;University of Sydney, Sydney, NSW, Australia;Cancer Genetics, Liverpool Hospital, Sydney, NSW, Australia;Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia;Children’s Medical Research Institute, University of Sydney, Westmead, NSW, Australia;Department of Health, Genetic Services of WA, Subiaco, WA, Australia;Department of Medicine, University of Melbourne, Melbourne, VIC, Australia;Genomic Medicine and Familial Cancer Clinic, Royal Melbourne Hospital, Melbourne, VIC, Australia;Faculty of Medicine and Health, University of Sydney, L2.22 The Quadrangle (A14), 2006, Sydney, NSW, Australia;Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia;Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia;Faculty of Medicine and Health, University of Sydney, L2.22 The Quadrangle (A14), 2006, Sydney, NSW, Australia;Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia;Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia;Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia;Genomics, Pathology Queensland, Brisbane, QLD, Australia;Familial Cancer Services, The Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia;Genetic Health Queensland, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia;Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, WA, Australia;Genetic Services of Western Australia, King Edward Memorial Hospital, Subiaco, WA, Australia;Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia;Monash Health Familial Cancer, Monash Health, Melbourne, VIC, Australia;Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia;Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia;Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia;Department of Medicine, University of Melbourne, Melbourne, VIC, Australia;Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia;Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia;Prince of Wales Clinical School, UNSW Medicine and Health, The University of New South Wales, Sydney, NSW, Australia;Hereditary Cancer Centre, Prince of Wales Hospital, Sydney, NSW, Australia;QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Brisbane, QLD, Australia;QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Brisbane, QLD, Australia;Australian Genomics, Melbourne, VIC, Australia;QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD 4006, Brisbane, QLD, Australia;Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia;Tasmanian Clinical Genetics Service, Royal Hobart Hospital, Hobart, TAS, Australia;Tasmanian Clinical Genetics Service, Royal Hobart Hospital, Hobart, TAS, Australia;School of Medicine and Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia;

关键词: Familial cancer;    Genetics;    Variants;    Whole-genome sequencing;    Diagnostic testing;    Health economics;   

DOI  :  10.1186/s13073-023-01223-1

 received in 2022-10-04, accepted in 2023-08-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMany families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer.MethodsThis multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken.ResultsPathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing.ConclusionsThese findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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